Structural Characterization and Assessment of Anti-Inflammatory Activities of Polyphenols and Depsidone Derivatives from Melastoma malabathricum subsp. normale

Abstract

The roots of Melastoma malabathricum subsp. normale (D. Don) Karst. Mey have been used in traditional ethnic medicine systems in China to treat inflammation-triggered ailments, such as trauma, toothache, and fever. Therefore, the aim of this study is to screen for compounds with anti-inflammatory activity in the title plant. The extract of M. malabathricum subsp. normale roots was separated using various chromatographic methods, such as silica gel, ODS C18, MCI gel, and Sephadex LH-20 column chromatography, as well as semi-preparative HPLC. One new complex tannin, named whiskey tannin D (1), and an undescribed tetracyclic depsidone derivative, named guanxidone B (2), along with nine known polyphenols (2–10) and three known depsidone derivatives (12–14) were obtained from this plant. The structures of all compounds were elucidated by extensive NMR and CD experiments in conjunction with HR-ESI-MS data. All these compounds were isolated from this plant for the first time. Moreover, compounds 1–4, 8, and 10–14 were obtained for the first time from the genus Melastoma, and compounds 1, 2, and 11–14 have not been reported from the family Melastomataceae. This is the first report of complex tannin and depsidone derivatives from M. malabathricum subsp. normale, indicating their chemotaxonomic significance to this plant. Compounds 1–12 were investigated for their anti-inflammatory activities on the production of the nitric oxide (NO) in lipopolysaccharide (LPS)-stimulated RAW264.7 cells, and compounds 1, 11, and 12 showed anti-inflammatory activities with IC50 values of 6.46 ± 0.23 µM, 8.02 ± 0.35 µM, and 9.82 ± 0.43 µM, respectively. The structure–activity relationship showed that the catechin at glucose C-1 in ellagitannin was the key to its anti-inflammatory activity, while CH3O- at C-16 of aromatic ring A in depsidone derivatives had little effect on its anti-inflammatory activity. The study of structure–activity relationships is helpful to quickly discover new anti-inflammatory drugs. The successful isolation and structure identification of these compounds, especially complex tannin 1, not only provide materials for the screening of anti-inflammatory compounds, but also provide a basis for the study of chemical taxonomy of the genus Melastoma.

Small Molecules as Anti‐inflammatory Agents: Molecular Mechanisms and Heterocycles as Inhibitors of Signaling Pathways

“…More recently, many researchers have reported natural products as anti‐inflammatory agents targeting different inflammatory pathways [103–106] …”

Recent advances on natural depsidones: sources, biosynthesis, structure-activity relationship, and bioactivities

“…This metabolite (IC 50 8.22 μM) displayed a noticeable NO production inhibition capacity in RAW 264.7 cells boosted by LPS compared to dexamethasone (IC 50 5.62 μM). In another study, He et al (2022) investigated Melastoma malabathricum subsp. normale roots utilizing SiO 2 /RP-18/Sephadex LH-20 CC/HPLC, resulting in a new derivative, guanxidone B ( 56 ) together with 12 , 51 , and 55 .…”

“…Compound 56 was structurally similar to 51 having C-4 CH 2 OH instead of C-4 CH 3 in 51 . It is noteworthy that 56 had better activity than 55 , indicating that CH 3 O at C-4 affected the activity ( He et al, 2022 ).…”

Curdepsidone A Induces Intrinsic Apoptosis and Inhibits Protective Autophagy via the ROS/PI3K/AKT Signaling Pathway in HeLa Cells

“…Depsidones are a class of polyphenolic polyketides formed via the oxidative coupling of esters of two polyketide benzoic acid derivatives [11]. They exhibit a variety of bioactivities such as cytotoxic [12,13], anti-inflammatory [14,15], antimicrobial [13,16,17], antimalarial [18], antioxidant [19], and antidiabetic [20] activities. Curdepsidones A-G, derivatives of depsidone, were first isolated from the secondary metabolites of a marine white croakerassociated fungus Curvularia sp.…”